Pathology Of The Liver And Gallbladder Flashcards
What is acute liver failure
Acute liver illness associated with encephalopathy and coagulopathy that occurs within 26 week of the initial liver injury in the absence of pre-existing liver disease.
•Most patients progress to coma within a week.
•Its is useful to know the interval between onset of symptoms and liver failure as this can point to the aetiology.
•Very rapid onset (formerly called fulminant hepatitis): due to drugs, toxins causing massive hepatic necrosis. Usually acetaminophen, but also autoimmune hepatitis, Hep A,B and E.
•Injury may be due to direct toxic injury or immune mediated.
•Rare causes include cancers (lymphoma, leukemias), abnormalities of blood flow, metabolic disorders.
What is ascites
Occurs due to cirrhosis in 85% cases.
•Detected clinically at >500ml of fluid
•It is usually a transudate
•Can seep through trans-diaphragmatic lymphatics to cause hydrothorax, particularly on the right
What are portosystemic shunts
eins around and within the rectum (manifest as hemorrhoids)
•Esophagogastric junction (producing varices)- bleeding leads to and death in 50% of cases
•Retroperitoneum and the falciform ligament of the liver (involving periumbilical and abdominal wall collaterals)-Caput medusae
What is splenomegaly
Enlargement up to 1000g
•May induce hypersplemism
•Sequestrates blood elements in expanded red pulps
What is hepatopulmonary syndrome
•Seen in 30% of patients with cirrhosis and portal hypertension
•Caused by the dilatation of intrapulmonary capillary and precapillary vessels
•Causes right to left shunting of blood leading to V/Q mismatch and hypoxemia which worsens in the upright position.
•Thought to be caused by reduced hepatic clearance of endothelin-1 which stimulates NO production.
What is portopulmonary hypertension
Pulmonary arterial hypertension arising in liver disease.
•Concomitant portal hypertension and excessive pulmonary vasoconstriction and vascular remodeling.
•Causes dyspnea on exertion and finger clubbing.
What is acute on chronic liver failure
Rapid hepatic decompensation in a patient with chronic hepatic failure.
•Hep D on chronic Hep B, or mutant Hep B on chronic hep B.
•Rapid weight loss or malnutrition in the patient with nonalcoholic hepatosteatosis
•Other causes are sepsis, acute cardiac failure or malignancy.
What is hepatitis A
Nonenveloped, positive strand RNA picornavirus
•Self limiting without chronicity
•Transmission is feco-oral although sexual transmission is possible
•The receptor for HAV on hepatocytes is HAVcr-1 (also known as TIM-1)
•It has no cytopathic effect
•Injury is caused by cytotoxic T-lymphocytes and NK cells
Incubation period is 2 to 6 weeks
•IgM appears with symptoms IgG appears during recovery conferring lifelog immunity.
•Complications include acute liver failure (0.1-0.3% of cases), cholestsasis, relapse, and immune mediated leukocytoclastic vasculitis, glomerulonephritis and cryoglobulinemia.
What is hepatitis B
Hep B may present as:
•Acute hepatitis followed by recovery and clearance of the virus
•Acute hepatic failure with massive liver necrosis
•Chronic hepatitis with or without progression to cirrhosis
•Asymptomatic, “healthy” carrier state
Prevalent in Africa, Asia and Western Pacific rim
•Has a parenteral mode of transmission as well as horizontal transmission
•Hepadnaviridae
•The virus has the following proteins:
•Hepatitis B surface antigen: envelope glycoproteins
•Hepatitis B core antigen: nucleocapsid protein
•Hepatitis Be Antigen: nuclear polypeptide
•HBV polymerase: DNA pol and reverse transcriptase
•Hepatitis B X protein: transcription transactivator: plays a role in hepatocellular carcinoma
Although cytopathic effect exists, most disease is caused by the host immune response.
•Strong interferon response by CD4+ and CD8+ cells is important for resolution of acute infection
•HBsAg: persists with viremia, present in chronic liver disease
•Anti-HBs: appears on resolution, denotes immunity
•IgM anti-HBc: Acute infection
•HBeAg, HBV DNA, HBV DNA pol: active replication, infectivity and chronicity
•Anti-Hbe: waning acute infection, not formed in chronic infection
Anorexia, fever, jaundice, and upper right quadrant pain
•Glomerulonephritis, polyarteritis nodosa- immune complex mediated
•Rarely acute liver failure occurs
•5-10% become chronic, chronicity and eventually hepatocellular carcinoma is inversely proportional to age of patient
•Vaccination is effective
•Treatment is with interferons and reverse transcriptase inhibitors
What is hepatitis C
It is the most common chronic blood-borne infection
•Flaviviridae family, genus Hepacivirus
•Parenteral and horizontal modes of transmission
•Pathogenesis:
•HCV RNA polymerase has poor fidelity leading to genomic instability & antigenic variability within one individual
•Evasion of IFN-mediated anti-viral response and repeated bouts of hepatic damage
What is hepatitis D
Hepatitis delta virus
•Replication is defective in the virus hence it causes infection only when encapsulated by HBsAg
What is autoimmune hepatitis
Chronic hepatitis of variable severity, histologically indistinguishable from chronic viral hepatitis
•Patients have variety of immunologic abnormalities
•Female predominance (70%)
•No serologic viral markers
•Elevated serum IgG >2.5 gm/dl
•High titers of autoantibodies (80%) including ANA, anti-smooth muscles. Increased frequency of HLA-B8 or HLA-DRw
•Other forms of autoimmune diseases may be present (60%), e.g. RA, Sjogren’s syndrome
•Overall risk for cirrhosis is 5%
•Rx: good response to immunosuppressive therapy
What is alcoholic liver disease
Alcohol is the fifth leading cause of death in the U.S. (many related to automobile accidents)
•3 forms of alcoholic liver disease:
• Hepatic steatosis
• Alcoholic hepatitis
• Alcoholic cirrhosis
What are the three forms of alcoholic liver disease
• Hepatic steatosis
• Alcoholic hepatitis
• Alcoholic cirrhosis
What is the pathogenesis of alcoholic liver
Alcohol-induced hepatocellular steatosis:
•Generation of excess NADH by alcohol dehydrogenase and acetaldehyde dehydrogenase leading to increased lipid biosynthesis
•Impaired assembly & secretion of lipoproteins
•Increased peripheral catabolism of fat
Alcohol-induced hepatocellular damage:
•Induction of cytochrome P-450
•Generation of free radicals
•Direct effect on microtubular and mitochondrial function and membrane fluidity
•Acetaldehyde induces lipid peroxidation and acetaldehyde-protein adduct formation, further disrupting cytoskeletal and membrane function
•Antigenic alteration of hepatocytes & hepatic proteins, inducing an immunologic attack
Alcohol-induced fibrosis:
•Multifactorial and poorly understood
•Other effects of alcohol:
•Malnutrition & vitamin deficiencies
•Impaired digestive function (chronic gastric and intestinal mucosal damage and pancreatitis)
What is alcoholic steatosis
Lipid droplets accumulate in hepatocytes
•2 histologic types:
•Microvesicular
•Macrovesicular
•Initially centrilobular
•Later panlobular
•Large (4-6 kg) soft yellow greasy appearance
•Completely reversible if there is abstention
What is alcoholic hepatitis
Hepatocyte swelling (ballooning) due to accumulation of fat and water, and cell necrosis
•Mallory bodies: characteristic eosinophilic cytoplasmic inclusions (cytokeratin intermediate filaments)
What is hepatic cirrhosis
Initially, the liver is yellow- tan, fatty and enlarged
•Eventually, it becomes brown, shrunken and non-fatty
•Fibrous septa become thicker and extend through sinusoids
What are clinical features of alcoholic liver disease
Hepatic steatosis
•Asymptomatic
•Mild ↑ serum bilirubin and alkaline phosphatase
•Alcoholic hepatitis
•Minimal to severe manifestations
•Nonspecific symptoms
•Increase in serum bilirubin, alkaline phosphatase, WBCs
•Alcoholic cirrhosis
•Similar to other forms of cirrhosis
